Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial

医学 彭布罗利珠单抗 易普利姆玛 临床终点 内科学 不利影响 队列 临床试验 实体瘤疗效评价标准 黑色素瘤 胃肠病学 外科 耐火材料(行星科学) 临床研究阶段 免疫疗法 癌症 天体生物学 物理 癌症研究
作者
Caroline Robert,Antoni Ribas,Jedd D. Wolchok,F. Stephen Hodi,Omid Hamid,Richard Kefford,Jeffrey S. Weber,Anthony M. Joshua,Wen-Jen Hwu,Tara C. Gangadhar,Amita Patnaik,Roxana Dronca,Hassane M. Zarour,Richard W. Joseph,Peter D. Boasberg,Bartosz Chmielowski,Christine Mateus,Michael A. Postow,Kevin Gergich,Jeroen Elassaiss‐Schaap
出处
期刊:The Lancet [Elsevier BV]
卷期号:384 (9948): 1109-1117 被引量:1726
标识
DOI:10.1016/s0140-6736(14)60958-2
摘要

The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma.In an open-label, international, multicentre expansion cohort of a phase 1 trial, patients (aged ≥18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule (1:1 final ratio) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. Primary endpoint was overall response rate (ORR) assessed with the Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) by independent central review. Analysis was done on the full-analysis set (all treated patients with measurable disease at baseline). This study is registered with ClinicalTrials.gov, number NCT01295827.173 patients received pembrolizumab 2 mg/kg (n=89) or 10 mg/kg (n=84). Median follow-up duration was 8 months. ORR was 26% at both doses--21 of 81 patients in the 2 mg/kg group and 20 of 76 in the 10 mg/kg group (difference 0%, 95% CI -14 to 13; p=0·96). Treatment was well tolerated, with similar safety profiles in the 2 mg/kg and 10 mg/kg groups and no drug-related deaths. The most common drug-related adverse events of any grade in the 2 mg/kg and 10 mg/kg groups were fatigue (29 [33%] vs 31 [37%]), pruritus (23 [26%] vs 16 [19%]), and rash (16 [18%] vs 15 [18%]). Grade 3 fatigue, reported in five (3%) patients in the 2 mg/kg pembrolizumab group, was the only drug-related grade 3 to 4 adverse event reported in more than one patient.The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options.Merck Sharp and Dohme.
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